Featured Publications
Human keratin 1/10‐1B tetramer structures reveal a knob‐pocket mechanism in intermediate filament assembly
Eldirany SA, Ho M, Hinbest AJ, Lomakin IB, Bunick CG. Human keratin 1/10‐1B tetramer structures reveal a knob‐pocket mechanism in intermediate filament assembly. The EMBO Journal 2019, 38: embj2018100741. PMID: 31036554, PMCID: PMC6545558, DOI: 10.15252/embj.2018100741.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionCircular DichroismCrystallography, X-RayCytoskeletonDynamic Light ScatteringHumansHydrophobic and Hydrophilic InteractionsIntermediate Filament ProteinsKeratin-1Keratin-10Models, MolecularMutation, MissenseProtein FoldingProtein Interaction Domains and MotifsProtein MultimerizationProtein Structure, QuaternaryProtein Structure, SecondarySkin DiseasesConceptsFilament assemblyN-terminal hydrophobic pocketIntermediate filament assemblyTetramer assemblyÅ structureÅ resolutionCircular dichroism measurementsTetramer formationAssembly mechanismHydrophobic faceHydrophobic pocketSecondary structureOctamer structureEpidermolytic palmoplantar keratodermaKeratin filamentsIntermediate filamentsMutationsPathogenic mutationsTetramer structureDichroism measurementsAtomic resolutionAssemblyBiochemical determinantsKeratin 1/10TetramerThe Crystal Structure of Yeast Fatty Acid Synthase, a Cellular Machine with Eight Active Sites Working Together
Lomakin IB, Xiong Y, Steitz TA. The Crystal Structure of Yeast Fatty Acid Synthase, a Cellular Machine with Eight Active Sites Working Together. Cell 2007, 129: 319-332. PMID: 17448991, DOI: 10.1016/j.cell.2007.03.013.Peer-Reviewed Original ResearchConceptsCatalytic siteCrystal structureAcyl carrier proteinPantetheine armActive siteCatalytic centerMacromolecular assembliesYeast fatty acid synthaseReaction chamberKetoacyl synthase domainWhole metabolic pathwaysTwo-dimensional diffusionAssemblyCarrier proteinSynthesisStructureComplexesCellular machinesMultiple stepsAcidSitesShellSubstrateA Conserved HEAT Domain within eIF4G Directs Assembly of the Translation Initiation Machinery
Marcotrigiano J, Lomakin I, Sonenberg N, Pestova T, Hellen C, Burley S. A Conserved HEAT Domain within eIF4G Directs Assembly of the Translation Initiation Machinery. Molecular Cell 2001, 7: 193-203. PMID: 11172724, DOI: 10.1016/s1097-2765(01)00167-8.Peer-Reviewed Original ResearchConceptsInternal ribosome entry siteTranslation initiation machineryInitiation machineryHEAT domainATP-dependent RNA helicase eIF4AStructure-based site-directed mutagenesisCap-independent translation initiationRNA helicase eIF4ASite-directed mutagenesisPicornaviral internal ribosome-entry siteRibosome entry siteRibosomal complex formationHelicase eIF4ATranslation initiationAlpha-helixEntry siteEIF4AMechanistic insightsX-ray structureComplex formationMachineryBiochemical resultsEssential componentDomainMutagenesisThe initiation of mammalian protein synthesis and mRNA scanning mechanism
Lomakin IB, Steitz TA. The initiation of mammalian protein synthesis and mRNA scanning mechanism. Nature 2013, 500: 307-311. PMID: 23873042, PMCID: PMC3748252, DOI: 10.1038/nature12355.Peer-Reviewed Original ResearchConceptsSmall ribosomal subunitTranslation initiationRibosomal subunitMammalian translation initiationProtein synthesisInitiator transfer RNAMammalian protein synthesisMultiple initiation factorsMRNA scanningTransfer RNAInitiation factorsInitiation codonConformational changesMessenger RNAFunctional implicationsEukaryotesDistinct stepsP siteSubunitsRNAFunctional stateEIF1ARibosomesEIF1CodonThe mechanism of inhibition of protein synthesis by the proline-rich peptide oncocin
Roy RN, Lomakin IB, Gagnon MG, Steitz TA. The mechanism of inhibition of protein synthesis by the proline-rich peptide oncocin. Nature Structural & Molecular Biology 2015, 22: 466-469. PMID: 25984972, PMCID: PMC4456192, DOI: 10.1038/nsmb.3031.Peer-Reviewed Original Research
2020
Structural properties of target binding by profilaggrin A and B domains and other S100 fused-type calcium-binding proteins
Hinbest AJ, Kim SR, Eldirany SA, Lomakin IB, Watson J, Ho M, Bunick CG. Structural properties of target binding by profilaggrin A and B domains and other S100 fused-type calcium-binding proteins. Journal Of Dermatological Science 2020, 100: 39-49. PMID: 32893105, PMCID: PMC7752840, DOI: 10.1016/j.jdermsci.2020.08.009.Peer-Reviewed Original ResearchAmino Acid SequenceAnnexin A2Binding SitesCrystallography, X-RayFilaggrin ProteinsHumansHydrophobic and Hydrophilic InteractionsIntermediate Filament ProteinsIntermediate FilamentsKeratinocytesKeratinsMolecular Docking SimulationMutationProtein BindingProtein Conformation, alpha-HelicalProtein DomainsProtein PrecursorsRecombinant ProteinsS100 Proteins
2017
Crystal Structure of the C-terminal Domain of Human eIF2D and Its Implications on Eukaryotic Translation Initiation
Vaidya AT, Lomakin IB, Joseph NN, Dmitriev SE, Steitz TA. Crystal Structure of the C-terminal Domain of Human eIF2D and Its Implications on Eukaryotic Translation Initiation. Journal Of Molecular Biology 2017, 429: 2765-2771. PMID: 28736176, PMCID: PMC5572308, DOI: 10.1016/j.jmb.2017.07.015.Peer-Reviewed Original ResearchMeSH KeywordsCrystallography, X-RayEukaryotic Initiation Factor-2HumansModels, MolecularPeptide Chain Initiation, TranslationalProtein ConformationProtein DomainsConceptsTranslation initiationProtein synthesisEukaryotic translation initiationSmall ribosomal subunitTranslation initiation factorInitiation factor 2C-terminal domainInitiation codon selectionInter-domain interactionsCellular protein synthesisRibosome recyclingCertain mRNAsInitiation factorsRibosomal subunitTerminal domainCodon selectionInitiator tRNAMolecular mechanismsΑ-subunitInitiation pathwayTerminal partAtomic detailStress conditionsEIF2DSecond domainCrystal Structure of the Human Ribosome in Complex with DENR-MCT-1
Lomakin IB, Stolboushkina EA, Vaidya AT, Zhao C, Garber MB, Dmitriev SE, Steitz TA. Crystal Structure of the Human Ribosome in Complex with DENR-MCT-1. Cell Reports 2017, 20: 521-528. PMID: 28723557, PMCID: PMC5551485, DOI: 10.1016/j.celrep.2017.06.025.Peer-Reviewed Original ResearchMeSH KeywordsCell Cycle ProteinsCrystallography, X-RayEukaryotic Initiation FactorsHumansOncogene ProteinsProtein Structure, QuaternaryRibosomesConceptsSmall ribosomal subunitTranslation initiationRibosomal subunitUnconventional translation initiationInitiation factor 1Cancer-related mRNAsTranslational controlHuman ribosomeTerminal domainReinitiation stepsRibosomesDimer interactsFunctional implicationsFactor 1SubunitsCrystal structureStriking similaritySpecific setComplexesHeterodimersProteinOncoproteinInitiationInteractsMRNA
2016
Structures of proline-rich peptides bound to the ribosome reveal a common mechanism of protein synthesis inhibition
Gagnon MG, Roy RN, Lomakin IB, Florin T, Mankin AS, Steitz TA. Structures of proline-rich peptides bound to the ribosome reveal a common mechanism of protein synthesis inhibition. Nucleic Acids Research 2016, 44: 2439-2450. PMID: 26809677, PMCID: PMC4797290, DOI: 10.1093/nar/gkw018.Peer-Reviewed Original ResearchAmino Acid SequenceAnimalsAnti-Bacterial AgentsAntimicrobial Cationic PeptidesBinding SitesCattleCrystallography, X-RayEscherichia coliInsect ProteinsModels, MolecularMolecular Sequence DataPeptides, CyclicProtein BindingProtein BiosynthesisRibosomesRNA, MessengerRNA, TransferSpecies SpecificityThermus thermophilus